Carvalho Claudia M B, Zhang Feng, Lupski James R
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Proc Natl Acad Sci U S A. 2010 Jan 26;107 Suppl 1(Suppl 1):1765-71. doi: 10.1073/pnas.0906222107. Epub 2010 Jan 13.
Gene duplications alter the genetic constitution of organisms and can be a driving force of molecular evolution in humans and the great apes. In this context, the study of genomic disorders has uncovered the essential role played by the genomic architecture, especially low copy repeats (LCRs) or segmental duplications (SDs). In fact, regardless of the mechanism, LCRs can mediate or stimulate rearrangements, inciting genomic instability and generating dynamic and unstable regions prone to rapid molecular evolution. In humans, copy-number variation (CNV) has been implicated in common traits such as neuropathy, hypertension, color blindness, infertility, and behavioral traits including autism and schizophrenia, as well as disease susceptibility to HIV, lupus nephritis, and psoriasis among many other clinical phenotypes. The same mechanisms implicated in the origin of genomic disorders may also play a role in the emergence of segmental duplications and the evolution of new genes by means of genomic and gene duplication and triplication, exon shuffling, exon accretion, and fusion/fission events.
基因复制会改变生物体的遗传构成，并且可能是人类和大猩猩分子进化的驱动力。在此背景下，对基因组疾病的研究揭示了基因组结构所起的关键作用，尤其是低拷贝重复序列（LCRs）或节段性重复序列（SDs）。事实上，无论其机制如何，LCRs都能介导或刺激重排，引发基因组不稳定，并产生易于快速分子进化的动态不稳定区域。在人类中，拷贝数变异（CNV）与诸如神经病变、高血压、色盲、不育等常见性状以及包括自闭症和精神分裂症在内的行为性状有关，还与许多其他临床表型中对HIV、狼疮性肾炎和牛皮癣的疾病易感性有关。与基因组疾病起源相关的相同机制，也可能在节段性重复序列的出现以及通过基因组和基因复制与三倍化、外显子改组、外显子增添以及融合/裂变事件产生新基因的进化过程中发挥作用。
